Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

A randomized controlled trial of the impact of support visits on self-isolation compliance: The Havering winter/spring support trial.

OBJECTIVES: Limited evidence exists on the policies to increase self-isolation compliance, with no experimental evidence. This trial aimed to evaluate the effect of a home visiting intervention in the London Borough of Havering on compliance with self-isolation guidance, relative to positive COVID-19 cases who received no home visits. DESIGN: Mixed method evaluation involving a two-arm randomized controlled trial (RCT) with an implementation and process evaluation. METHODS: A total of 3878 cases who tested positive for COVID-19 were randomly allocated with equal probability to receive home visits from Havering outreach team staff (n = 1946) or to a control group (n = 1932) who did not receive home visits. Randomization was implemented through a spreadsheet consisting of random numbers generated online that was used to randomly allocate cases to treatment and control. Check-in calls were conducted by a separate blinded contact tracing team on day six of isolation to measure successful self-isolation compliance. The primary intention-to-treat (ITT) analysis was conducted on 3860 cases as 18 patients were excluded from analysis because of the missing outcome data. For the implementation and process evaluation, qualitative, semi-structured, one-to-one interviews were conducted with trial participants in the treatment arm of the RCT (n = 15) and stakeholders within the London Borough of Havering's Adult Social Care and Health Team (n = 8). Qualitative data was analysed thematically using a framework approach. RESULTS: Positive cases who were allocated to receive the home visiting intervention (n = 1933) were more likely to report successful self-isolation compared to those allocated to the control group (n = 1927), an effect that was statistically significant (odds ratio 1.204 [95% CI: 1.052, 1.377]; absolute probability difference: 4.1 percentage points [95% CI: 1.2-6.9]). The implementation and process evaluation found that a key driver of compliance was altruistic motivation based on its perceived importance for protecting the community with some participants also reporting the potential of being caught not complying as a driving factor. Participants also reported that the intervention helped them 'feel supported', provided them with information about practical and financial support, and clarified their understanding or increased their awareness of self-isolation and COVID-19 guidance. No harms were reported from this trial. The trial was registered at the ISRCTN registry, number ISRCTN10030612. CONCLUSIONS: A home-visiting intervention conducted between January and March 2022 increased the self-isolation compliance of positive COVID-19 cases allocated to receive home visits. The implementation and process evaluation highlighted that the intervention increased individuals' motivation to comply with guidance, and addressed some barriers associated with opportunity and capability to comply. This trial provides much-needed evidence to inform the policy and intervention design to support public health and social measures in future outbreak scenarios.

An online RCT on behavioural expectations effects of COVID-19 certification policies in England.

Objective: The aim of this study was to compare the effects of different types of COVID-19 certification policy on subsequent behavioural expectations. Design: 4 × 2 between-subjects pre-registered randomised controlled trial. Method: In August 2022, participants (n = 2726) in England were presented with a scenario describing a rise in COVID-19 infections and the introduction of new protective measures. The protective measures described varied with regards to the setting (healthcare vs. recreational) and the type of policy (no certification vs. vaccination vs. vaccination or free Lateral Flow test vs. vaccination or Lateral Flow test at personal cost). Participants then answered questions on their expectations to receive another dose of the COVID-19 vaccine, to receive the seasonal influenza vaccine and to adhere to other protective behaviours following the announcement, as well as questions based on Self-Determination Theory, COVID-19 vaccine hesitancy and broader vaccine hesitancy. Results: We found no main effects of setting or type of certification on expectation to receive the next dose of the COVID-19 vaccine, to receive the seasonal influenza vaccine, or to adhere to other protective measures, when controlling for baseline expectations. Conclusions: These findings suggest that it is unlikely that the concept of certification, however it is framed, alters inclinations in the English population towards COVID-19 and seasonal flu vaccination or inclinations towards adhering to other protective behaviours within settings to which certification would apply. These findings are based on a hypothetical scenario and should be interpreted with caution.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation.

Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study.

PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Growth recovery and faltering through early adolescence in low- and middle-income countries: Determinants and implications for cognitive development.

Child chronic undernutrition, as measured by stunting, is prevalent in low- and middle-income countries and is among the major threats to child development. While stunting and its implications for cognitive development have been considered irreversible beyond early childhood there is a lack of consensus in the literature on this, as there is some evidence of recovery from stunting and that this recovery may be associated with improvements in cognition. Less is known however, about the drivers of growth recovery and the aspects of recovery linked to cognitive development. In this paper we investigate the factors associated with growth recovery and faltering through age 12 years and the implications of the incidence, timing, and persistence of post-infancy recovery from stunting for cognitive development using longitudinal data from Ethiopia, India, Peru, and Vietnam. We find that the factors most systematically associated with accelerated growth both before and after early childhood and across countries include mother's height, household living standards and shocks, community wages, food prices, and garbage collection. Our results suggest that post-infancy recovery from stunting is more likely to be systematically associated with higher achievement scores across countries when it is persistent and that associations between growth trajectories and cognitive achievement in middle childhood do not persist through early adolescence across countries. Overall, our findings indicate that growth after early childhood is responsive to changes in the household and community environments and that growth promotion after early childhood may yield improvements in child cognitive development.

Disparities in children's vocabulary and height in relation to household wealth and parental schooling: A longitudinal study in four low- and middle-income countries.

Children from low socio-economic status (SES) households often demonstrate worse growth and developmental outcomes than wealthier children, in part because poor children face a broader range of risk factors. It is difficult to characterize the trajectories of SES disparities in low- and middle-income countries because longitudinal data are infrequently available. We analyze measures of children's linear growth (height) at ages 1, 5, 8 and 12y and receptive language (Peabody Picture Vocabulary Test) at ages 5, 8 and 12y in Ethiopia, India, Peru and Vietnam in relation to household SES, measured by parental schooling or household assets. We calculate children's percentile ranks within the distributions of height-for-age z-scores and of age- and language-standardized receptive vocabulary scores. We find that children in the top quartile of household SES are taller and have better language performance than children in the bottom quartile; differences in vocabulary scores between children with high and low SES are larger than differences in the height measure. For height, disparities in SES are present by age 1y and persist as children age. For vocabulary, SES disparities also emerge early in life, but patterns are not consistent across age; for example, SES disparities are constant over time in India, widen between 5 and 12y in Ethiopia, and narrow in this age range in Vietnam and Peru. Household characteristics (such as mother's height, age, and ethnicity), and community fixed effects explain most of the disparities in height and around half of the disparities in vocabulary. We also find evidence that SES disparities in height and language development may not be fixed over time, suggesting opportunities for policy and programs to address these gaps early in life.

Growth trajectories from conception through middle childhood and cognitive achievement at age 8 years: Evidence from four low- and middle-income countries.

Child chronic malnutrition is endemic in low- and middle-income countries and deleterious for child development. Studies investigating the relationship between nutrition at different periods of childhood, as measured by growth in these periods (growth trajectories), and cognitive development have produced mixed evidence. Although an explanation of this has been that different studies use different approaches to model growth trajectories, the differences across approaches are not well understood. Furthermore, little is known about the pathways linking growth trajectories and cognitive achievement. In this paper, we develop and estimate a general path model of the relationship between growth trajectories and cognitive achievement using data on four cohorts from Ethiopia, India, Peru, and Vietnam. The model is used to: a) compare two of the most common approaches of modelling growth trajectories in the literature, namely the lifecourse plot and the conditional body size model, and b) investigate the potential channels via which the association between growth in each period and cognitive achievement manifests. We show that the two approaches are expected to produce systematically different results that have distinct interpretations. Results suggest that growth from conception through age 1 year, between age 1 and 5 years, and between 5 and 8 years are each positively and significantly associated with cognitive achievement at age 8 years and that this may be partly explained by the fact that faster-growing children start school earlier. We also find that a significant share of the association between early growth and later cognitive achievement is mediated through growth in interim periods.